Departament de Química Inorgànica i Orgànica, Universitat Jaume I, Avda. Sos Baynat s/n 12080 Castelló, Spain.
Institute of Pharmacy and Biochemistry, University of Mainz, Staudinger Weg 5, 55099 Mainz, Germany.
Bioorg Med Chem. 2018 Sep 1;26(16):4624-4634. doi: 10.1016/j.bmc.2018.07.015. Epub 2018 Jul 10.
A family of dipeptidyl enoates has been prepared and tested against the parasitic cysteine proteases rhodesain, cruzain and falcipain-2 related to sleeping sickness, Chagas disease and malaria, respectively. They have also been tested against human cathepsins B and L1 for selectivity. Dipeptidyl enoates resulted to be irreversible inhibitors of these enzymes. Some of the members of the family are very potent inhibitors of parasitic cysteine proteases displaying k (Ms) values of seven orders of magnitude. In vivo antiprotozoal testing was also performed. Inhibitors exhibited IC values in the micromolar range against Plasmodium falciparum, Trypanosoma brucei, Trypanosoma cruzi and even more promising lower values against Leishmania donovanii.
已经制备了一组二肽烯酸酯，并对与昏睡病、恰加斯病和疟疾分别相关的寄生虫半胱氨酸蛋白酶 rhodesain、cruzain 和 falcipain-2 进行了测试。它们还针对人组织蛋白酶 B 和 L1 进行了选择性测试。二肽烯酸酯对这些酶表现出不可逆抑制作用。该家族的一些成员是寄生虫半胱氨酸蛋白酶的非常有效的抑制剂，对寄生虫半胱氨酸蛋白酶的抑制常数 (K (Ms)) 值达到了七个数量级。还进行了体内抗原生动物测试。抑制剂对恶性疟原虫、布氏锥虫、克氏锥虫的 IC 值在微摩尔范围内，对利什曼原虫的抑制作用更有前景，IC 值更低。
